Anopheles gambiae s.s. the principal Afrotropical vector mosquito for malignant human malaria. The inherent ability of mosquitoes to transmit disease is largely a consequence of a lifestyle which depends upon the acquisition of blood meals for nutrition and reproduction. In this regard, An. gambiae s.s.is an especially potent disease vector because it prefers to take blood meals from humans whenever possible, a host-seeking phenotype termed anthropophily. The sensory modality of olfaction guides host-seeking behavior in mosquitoes, and is the process whereby host-specific chemical cues are transduced by specifically-tuned chemoreceptors in the mosquito's chemosensory organs. Every class and type of chemoreceptor displays a discreet range of chemicals to which it responds, and the range of chemical-tuning comprised within a fly's chemoreceptor repertoire has been shown to coincide with an olfactory-driven phenotype. Therefore, a high resolution examination of chemoreceptor variation among An. gambiae, and between a phenotypically- divergent mosquito species should better elucidate the chemoreceptive foundations for anthropophily. The proposed studies seek to decode the molecular bases of anthropophilic host-seeking behavior in An. gambiae by harnessing next generation sequencing (NGS) technology to quantitatively characterize transcriptional variation within the chemosensory tissues of mosquitos that differ markedly in their blood- feeding phenotypes. The first comparison will investigate chemoreceptor variation in An. gambiae following bloodfeeding, a time period during which these mosquitoes become refractory to host-seeking. These results will then inform the second comparative study which will focus on the chemosensory transcriptome of Anopheles quadriannulatus, a notably less-anthropophilic sibling species to An. gambiae. Taken together, these comparative studies will highlight specific sets of chemoreceptors that may mediate anthropophilic host- seeking behavior in An. gambiae. The receptors identified here will lend themselves to further functional characterization and could facilitate more-targeted vector control strategies. Ultimately, the results of these studies will not only highlight a putative chemosensory basis for anthropophily, but will also point to promising targets for a new generation of chemical agents that act as potent attractants or repellents for anopheline mosquitoes.